Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19109 | 57550;57551;57552 | chr2:178597757;178597756;178597755 | chr2:179462484;179462483;179462482 |
| N2AB | 17468 | 52627;52628;52629 | chr2:178597757;178597756;178597755 | chr2:179462484;179462483;179462482 |
| N2A | 16541 | 49846;49847;49848 | chr2:178597757;178597756;178597755 | chr2:179462484;179462483;179462482 |
| N2B | 10044 | 30355;30356;30357 | chr2:178597757;178597756;178597755 | chr2:179462484;179462483;179462482 |
| Novex-1 | 10169 | 30730;30731;30732 | chr2:178597757;178597756;178597755 | chr2:179462484;179462483;179462482 |
| Novex-2 | 10236 | 30931;30932;30933 | chr2:178597757;178597756;178597755 | chr2:179462484;179462483;179462482 |
| Novex-3 | None | None | chr2:None | chr2:None |
Information
Reported SAVs
| SNV | RS | DUET |
PolyPhen-2 |
Condel |
Rhapsody |
REVEL |
MVP |
Source |
MAF |
Disease |
Zygosity |
Site annotation |
mCSM PPI |
Predicted PPI site |
Comments |
AFR |
AMR |
AMS |
ASJ |
EAS |
EUR |
FIN |
MDE |
NFE |
SAS |
OTH |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | None | None | 0.973 | N | 0.502 | 0.159 | 0.260249123532 | gnomAD-4.0.0 | 1.59251E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85981E-06 | 0 | 0 |
| V/M | rs945083650  |
None | 0.999 | N | 0.501 | 0.329 | 0.269111216191 | gnomAD-4.0.0 | 9.5822E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 3.54108E-04 | None | 0 | 0 | 0 | 0 | 0 |
Saturation Mutagenesis
SAV |
AlphaMissense (IC) |
AlphaMissense Class (IC) |
AlphaMissense (N2AB) |
AlphaMissense Class (N2AB) |
mCSM |
mCSM class |
PolyPhen-2 |
PolyPhen-2 Class |
Rhapsody |
Rhapsody Class |
Condel |
Condel Score |
Site annotation |
mCSM PPI |
Predicted PPI site |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.3739 | ambiguous | 0.5703 | pathogenic | -0.981 | Destabilizing | 0.973 | D | 0.502 | neutral | N | 0.475100879 | None | None | I |
| V/C | 0.858 | likely_pathogenic | 0.9193 | pathogenic | -0.815 | Destabilizing | 1.0 | D | 0.53 | neutral | None | None | None | None | I |
| V/D | 0.6405 | likely_pathogenic | 0.8011 | pathogenic | -0.654 | Destabilizing | 0.999 | D | 0.688 | prob.neutral | None | None | None | None | I |
| V/E | 0.5375 | ambiguous | 0.7474 | pathogenic | -0.693 | Destabilizing | 0.998 | D | 0.574 | neutral | N | 0.464979886 | None | None | I |
| V/F | 0.3756 | ambiguous | 0.5336 | ambiguous | -0.766 | Destabilizing | 1.0 | D | 0.525 | neutral | None | None | None | None | I |
| V/G | 0.5052 | ambiguous | 0.6956 | pathogenic | -1.237 | Destabilizing | 0.998 | D | 0.595 | neutral | N | 0.455728113 | None | None | I |
| V/H | 0.8384 | likely_pathogenic | 0.9241 | pathogenic | -0.658 | Destabilizing | 1.0 | D | 0.667 | neutral | None | None | None | None | I |
| V/I | 0.0967 | likely_benign | 0.117 | benign | -0.411 | Destabilizing | 0.98 | D | 0.499 | neutral | None | None | None | None | I |
| V/K | 0.7075 | likely_pathogenic | 0.8589 | pathogenic | -0.922 | Destabilizing | 0.999 | D | 0.599 | neutral | None | None | None | None | I |
| V/L | 0.4401 | ambiguous | 0.6118 | pathogenic | -0.411 | Destabilizing | 0.973 | D | 0.518 | neutral | N | 0.499151175 | None | None | I |
| V/M | 0.2162 | likely_benign | 0.3374 | benign | -0.416 | Destabilizing | 0.999 | D | 0.501 | neutral | N | 0.505597144 | None | None | I |
| V/N | 0.4139 | ambiguous | 0.5856 | pathogenic | -0.699 | Destabilizing | 0.999 | D | 0.683 | prob.neutral | None | None | None | None | I |
| V/P | 0.8517 | likely_pathogenic | 0.9269 | pathogenic | -0.564 | Destabilizing | 1.0 | D | 0.63 | neutral | None | None | None | None | I |
| V/Q | 0.5695 | likely_pathogenic | 0.7393 | pathogenic | -0.875 | Destabilizing | 1.0 | D | 0.633 | neutral | None | None | None | None | I |
| V/R | 0.7196 | likely_pathogenic | 0.8569 | pathogenic | -0.373 | Destabilizing | 0.999 | D | 0.695 | prob.neutral | None | None | None | None | I |
| V/S | 0.3703 | ambiguous | 0.5462 | ambiguous | -1.182 | Destabilizing | 0.983 | D | 0.488 | neutral | None | None | None | None | I |
| V/T | 0.2275 | likely_benign | 0.328 | benign | -1.109 | Destabilizing | 0.398 | N | 0.247 | neutral | None | None | None | None | I |
| V/W | 0.9409 | likely_pathogenic | 0.974 | pathogenic | -0.894 | Destabilizing | 1.0 | D | 0.697 | prob.neutral | None | None | None | None | I |
| V/Y | 0.7943 | likely_pathogenic | 0.8858 | pathogenic | -0.615 | Destabilizing | 1.0 | D | 0.531 | neutral | None | None | None | None | I |
Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.